Role of Polo-Like Kinase 4 (PLK4) in Epithelial Cancers and Recent Progress in its Small Molecule Targeting for Cancer Management.

The polo-like kinases (PLKs) are a family of serine/threonine kinases traditionally linked to cell-cycle regulation. A structurally unique member of this family, PLK4, has been shown to regulate centriole duplication during the cell cycle via interactions with a variety of centrosomal proteins. Recent findings suggest that PLK4 is overexpressed in various human cancers and associated with poor cancer prognosis. Although several studies have shown that PLK4 inhibition may lead to cancer cell death, the underlying mechanisms are largely unknown. In this review, we discuss the structure, localization, and function of PLK4, along with the functional significance of PLK4 in epithelial cancers and some preliminary work suggesting a role for PLK4 in the key cancer progression process epithelial-mesenchymal transition. We also discuss the potential of PLK4 as a druggable target for anticancer drug development based on critical analysis of the available data of PLK4 inhibitors in preclinical development and clinical trials. Overall, the emerging data suggest that PLK4 plays an essential role in epithelial cancers and should be further explored as a potential biomarker and/or therapeutic target. Continued detailed exploration of available and next-generation PLK4 inhibitors may provide a new dimension for novel cancer therapeutics following successful clinical trials. ©2021 American Association for Cancer Research.